Synthesis of halogenated azo-aspirin analogues from natural product derivatives as the potential antibacterial agents.
Synthesis of halogenated azo-aspirin analogues from natural product derivatives as the potential antibacterial agents.
- Natural Product Research, 33(24), p.3507-3514, 2019 .
Chemical modification of medicines from natural product-based molecules has become of interest in recent years. In this study, a series of halogenated azo derivatives 1a-d were synthesised via coupling reaction, followed by Steglich esterification with aspirin (a natural product derivative)to form azo derivatives 2a-d. While, halogenated azo-aspirin 3a-d were synthesised via direct coupling reaction of aspirin and diazonium salt. Bacteriostatic activity was demonstrated against E. coli and S. aureus via turbidimetric kinetic method. Compound 3a-d showed excellent antibacterial activities against E. coli (MIC 75-94 ppm)and S. aureus (MIC 64-89 ppm)compared to ampicillin (MIC 93 and 124 ppm respectively), followed by 1a-d and 2a-d. The presence of reactive groups of -OH, N=N, C=O and halogens significantly contribute excellent interaction towards E. coli and S. aureus. Molecular dockings analysis of 3a against MIaC protein showed binding free energy of ?7.2 kcal/mol (E. coli)and ?6.6 kcal/mol (S. aureus).
ASPIRIN
AZO
TURBIDIMETRIC
CHEMICAL MODIFICATION
ANTIBACTERIAL
Chemical modification of medicines from natural product-based molecules has become of interest in recent years. In this study, a series of halogenated azo derivatives 1a-d were synthesised via coupling reaction, followed by Steglich esterification with aspirin (a natural product derivative)to form azo derivatives 2a-d. While, halogenated azo-aspirin 3a-d were synthesised via direct coupling reaction of aspirin and diazonium salt. Bacteriostatic activity was demonstrated against E. coli and S. aureus via turbidimetric kinetic method. Compound 3a-d showed excellent antibacterial activities against E. coli (MIC 75-94 ppm)and S. aureus (MIC 64-89 ppm)compared to ampicillin (MIC 93 and 124 ppm respectively), followed by 1a-d and 2a-d. The presence of reactive groups of -OH, N=N, C=O and halogens significantly contribute excellent interaction towards E. coli and S. aureus. Molecular dockings analysis of 3a against MIaC protein showed binding free energy of ?7.2 kcal/mol (E. coli)and ?6.6 kcal/mol (S. aureus).
ASPIRIN
AZO
TURBIDIMETRIC
CHEMICAL MODIFICATION
ANTIBACTERIAL